Abstract 5718: Rab34 is downregulated in human prostate cancer tissue
Authors: Ines Benedetti, Lia Barrios, Juan Rebollo
Journal: Cancer Research (2022)

Abstract Background: Rab34 encodes a protein belonging to the Rab family of proteins, which are small GTPases important in regulating signal transduction and cellular processes. A potential role of Rab34 in cancer has been suggested, but few studies have reported its function in human epithelial cancers. It was reported that prostate cancer (PCa) patients were more prone to biochemical recurrence when Rab34 was downregulated in PCa tissue compared with benign prostate tissue (BPT), being negatively associated with miR-148, a miRNA that increased the growth in cell lines and was up-regulated in PCa samples. Rab34 is a putative target gene for miR-9. We aimed to explore the Rab34 and miR-9 expression in PCa using a bioinformatic analysis, however, the mere presence of miRNA-binding sites is insufficient for predicting target regulation, and therefore, we also analyzed Rab34 expression in BPT and PCa tissues. Design: The expression of miR9-5p and Rab34 mRNA was explored in the tumor tissues of the Cancer Genome Atlas (TCGA) through the bioinformatics tools of the dbDEMC2 and GEPIA2 web servers, and additional evidence of miR-9/Rab34 interaction was sought in the miRTarBase of experimentally validated microRNA-target interactions. Two pathologists evaluated Rab34 immunohistochemical expression in localized PCa and BPT in a prostate tissue microarray. For each spot an H-score was obtained by microscopic assessment of epithelial cells with positive staining. Differences in Rab34 expression were found by comparing H-Scores between BPT and PCa tissues using Mann-Whitney test, a p value less than 0.05 was considered statistically significant. Results: The analysis of miR-9 and Rab34 expression in the TCGA showed that Rab34 has a diverse expression in tumor tissues, being downregulated in colon, rectum and PCa, and upregulated in lymphoma, leukemia and pancreatic adenocarcinoma. On the other hand, miR-9 was upregulated in PCa and downregulated in pancreatic adenocarcinoma. There were no experimental evidence supporting the miR-9/Rab34 interaction in PCa tissues from the miRTarBase. However, most of the breast cancer datasets showed a negative correlation in the expression of both genes. Rab34 expression at protein level was assessed in 123 tissue cores representing PCa, and 86 tissue cores representing BPT. In cores with PCa mean Rab34 expression was significantly lower than the mean Rab34 expression in cores with BPT (p less than 0.0001). There was a lower mean staining score in PCa (87.3, 95% CI: 73.78 - 100.9), compared to BPT (156.3, 95% CI: 144 - 168.5). Conclusions: Our study shows that Rab34 is downregulated in PCa tissue. These findings are in accordance to a previous report that associated its lower expression to worse prognosis and tumor recurrence. The downregulation of Rab34 in PCa tissue might be related to overexpression of its putative microRNA, miR-9. Additional studies to detect the in situ expression of miR-9 in PCa are in progress to validate these results. Citation Format: Ines Benedetti, Lia Barrios, Juan Rebollo. Rab34 is downregulated in human prostate cancer tissue [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5718.